Karawajczyk Anna, Drgan Viktor, Medic Nevenka, Oboh Ganiyu, Passamonti Sabina, Novic Marjana
National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.
Biochem Pharmacol. 2007 Jan 15;73(2):308-20. doi: 10.1016/j.bcp.2006.09.024. Epub 2006 Sep 29.
Bilitranslocase is a plasma membrane carrier firstly identified on the sinusoidal (vascular) domain of liver cells and later on also in the gastric epithelium. It transports diverse organic anions, such as bilirubin, some phthaleins and many dietary anthocyanins, suggesting that it could play a role both in the absorption of flavonoids from dietary sources and in their hepatic metabolism. This work was aimed at characterising the interaction of bilitranslocase with flavonols, a flavonoid sub-class. The results obtained show that, contrary to anthocyanins, flavonol glycosides do not interact with the carrier, whereas just some of the corresponding aglycones act as relatively poor ligands to bilitranslocase. These data point to a clear-cut discrimination between anthocyanins and flavonols occurring at the level of the bilitranslocase transport site. A quantitative structure-activity relationship based on counter propagation artificial neural network modelling was undertaken in order to shed light on the nature of flavonoid interaction with bilitranslocase. It was found that binding relies on the ability to establish hydrogen bonds, ruling out the involvement of charge interactions. This requisite might be at the basis of the discrimination between anthocyanins and flavonols by bilitranslocase and could lie behind some aspects of the distinct pharmacokinetic properties of anthocyanins and flavonols in mammals.
胆红素转运蛋白是一种首先在肝细胞的窦状（血管）区域被鉴定出来的质膜载体，后来在胃上皮细胞中也被发现。它能转运多种有机阴离子，如胆红素、一些酞类化合物和许多膳食花色苷，这表明它可能在从膳食来源吸收黄酮类化合物及其肝脏代谢过程中都发挥作用。这项工作旨在表征胆红素转运蛋白与黄酮醇（一种黄酮类亚类）之间的相互作用。所获得的结果表明，与花色苷不同，黄酮醇苷不与该载体相互作用，而只有一些相应的苷元作为胆红素转运蛋白相对较差的配体。这些数据表明在胆红素转运蛋白转运位点水平上，花色苷和黄酮醇之间存在明显的区分。为了阐明黄酮类化合物与胆红素转运蛋白相互作用的本质，基于反向传播人工神经网络建模进行了定量构效关系研究。结果发现，结合依赖于建立氢键的能力，排除了电荷相互作用的参与。这一必要条件可能是胆红素转运蛋白区分花色苷和黄酮醇的基础，并且可能是花色苷和黄酮醇在哺乳动物中不同药代动力学特性某些方面的背后原因。
